Tibial Hemimelia (TH) is a lethal congenital disorder in cattle characterized by severe and lethal deformities in newborn calves, including multiple skeletal deformities such as twisted rear legs with fused joints, large abdominal hernias and/or skull deformities. Often, such a calf is born dead, or if it survives birth cannot stand to nurse and must be destroyed, resulting in economic loss for owners.
TH was first described in Galloway cattle in the 1960's and in Shorthorn cattle in 2000. Since that time there have been hundreds of calves identified with TH. Extensive breeding and pedigree studies (see Marron et al. 2005; Ojo et al., 1974; Lapointe et al. 2000) have revealed that TH has an autosomal recessive mode of inheritance. For the TH phenotype to be expressed, a calf must have inherited the defective gene from both parents. A calf that expresses the phenotype is “homozygous” for the mutant TH gene, and the parents of such a calf are “heterozygous carriers” for the mutant TH gene. It is virtually impossible in the absence of planned breeding studies or test matings to classify whether a normal appearing individual is a heterozygous carrier of the mutant TH gene or is homozygous for the normal allele. Genetic screening is beneficial in avoiding loss of genetic resources due to culling based only on pedigree.
Because heterozygous individuals appear normal, carriers of the trait cannot be identified by eye, and instead exhaustive and time-consuming familial analysis must be done in order to identify potential carrier individuals. There is a need in the art for screens that can identify heterozygous carriers of TH by genetic testing to facilitate a breeding program that eliminates the genetic defect from the population. Such a screen requires an understanding of the genetic basis of the defect, including identification of the causative mutation within the DNA sequence. The present invention discloses a mutation associated with TH and provides a genetic test to determine whether apparently normal individuals carry a defective gene associated with TH. The present invention enables testing of individuals to determine whether an individual is a carrier. Individuals that are carriers can be removed from the breeding population, thereby facilitating removal of this genetic defect from the population.
While dramatic culling of suspected carriers would reduce the frequency of the mutation responsible for TH, such culling is long, expensive and can result in unnecessary reduction of beneficial genetic traits, as many of the culled animals would not be carriers of the mutation. Accordingly, there is a need in the art for a diagnostic or genetic screening test to determine whether or not an animal is a carrier of the mutation responsible for TH. The present invention provides materials and methods for screening animals to determine whether an animal is a heterozygous carrier of the mutant allele responsible for TH.